Sotorasib for non-small cell lung cancer — current options and perspectives

Abstract

KRAS regulates several cellular processes, such as cell proliferation, cell cycle regulation, metabolic changes, cell survival, and cell differentiation. Abnormalities in the KRAS gene are found in approximately 30% of patients with non-small cell lung cancer, usually in patients diagnosed with nonsquamous cancer and more often in Caucasian patients, women, and smokers. The p.G12C variant is most frequently found in KRAS-positive patients. Sotorasib is the first drug approved for this population. The superiority of sotorasib over docetaxel after failure of immunochemotherapy was demonstrated in the CodeBreak 200 phase III study for the primary endpoint -median progression-free survival was 5.6 months [95% confidence interval (CI) 4.3-7.8] vs. 4.5 months (3.0-5.7); hazard ratio = 0.66 (95% CI 0.51-0.86; p = 0-0017), while the 12-month progression-free survival rate was 24.8% for sotorasib and 10.1% for docetaxel. Currently, sotorasib monotherapy, at an initial dose of 960 mg/day, is indicated for use in adults with advanced non-small cell lung cancer with the KRAS p.G12C mutation who have experienced disease progression after at least one previous line of systemic treatment. More randomized trials are needed to determine the optimal place of sotorasib in the systemic treatment sequence in this patient population.